This proposed phase II study will evaluate the efficacy of systemic angiogenesis inhibition combined with regional, hepatic arterial chemotherapy in patients with unresectable primary hepatic malignancy. Specifically, this protocol targets patients with unresectable hepatocellular carcinoma (HCC) or intrahepatic (peripheral) cholangiocarcinoma (ICC) for continuous infusion of floxuridine (FUDR) combined with systemic bevacizumab. Prior work has established the safety and efficacy of regional intrahepatic FUDR in this patient population. The current proposal is based on the hypothesis that the growth and progression of primary liver cancer are dependent on pro-angiogenic processes, the inhibition of which will enhance delivery of cytotoxic chemotherapy and improve its efficacy. A total of 45 patients will undergo placement of a hepatic artery infusion pump followed by continuous intrahepatic FUDR (0.16mg/kg) + dexamethasone (1mg/m2/kg/day) combined with systemic bevacizumab (5mg/kg) on a 4-week cycle. The calculated sample size will provide 90% power to detect a 50% improvement in time to progression over baseline therapy with intrahepatic chemotherapy alone. This study will also investigate the utility of dynamic contrast enhanced MRI scans (DCE-MRI) for assessing tumor perfusion kinetics (perfusion and permeability) prior to treatment, for monitoring these changes during treatment and for correlating these findings with radiographic tumor response. The study design allows for radiographic examination of the changes in tumor perfusion kinetics due to angiogenesis inhibition, both alone and in combination with cytotoxic chemotherapy. This proposal evaluates a promising treatment approach for patients with unresectable primary liver cancer, which is increasing in incidence, is associated with poor survival and for which effective treatments are limited. The current study therefore addresses a significant public health concern. Additionally, however, the proposed treatment represents a novel application of anti-angiogenic therapy with potential application for treating other malignancies. This study will also yield important data on an emerging functional imaging technique for assessing the efficacy of angiogenesis inhibition, the need for which has become increasingly clear. Furthermore, several important clinical issues are addressed by the proposed correlative studies, the results of which would be of broad general interest in clinical oncology. [unreadable] [unreadable] [unreadable]